OBJECTIVE: To examine the effect of pregnancy and lactation on variables known to influence the susceptibility of the mammary gland to carcinogenesis. APPROACH: Epidemiological studies show that breast cancer risk is higher in nulliparous than in parous women whose first pregnancy occurred at an early age. It has been shown that induction of rat mammary carcinomas by exposure to 7,12-dimethylbenz(a)anthracene depends upon the degree of differentiation of the gland and is prevented if the exposure is preceded by pregnancy and lactation. Our evidence suggests that this rat system can provide an excellent model for exploring the mechanisms involved in diminished susceptibility of the mammary gland to carcinogenesis. We propose to examine if the followin are related to diminished susceptibility. The level of DNA synthesis in the mammary epithelium; changes in the DNA excision repair of the mammary gland. The gland of young virgins will be hormonally differentiated in order to determine whether changes in those parameters are induced only by differentiation of the gland or whether full pregnancy exclusively is necessary for rendering the gland refractory to neoplastic transformation.